Recombinant human leukemia inhibitory factor (rhLIF) produced by Escherichia coli was administered subcutaneously (sc) to rhesus monkeys at doses of 2, 10, and 50 micrograms/kg body weight/d for 14 days to assess its biologic activities in vivo. Serum levels of positively regulated acute phase proteins (APP) (C-reactive protein, alpha 1-antitrypsin, haptoglobin, and ceruloplasmin) were increased, whereas the negatively regulated APP prealbumin decreased in response to rhLIF treatment. During the second week of treatment, blood platelet counts began to increase, resulting in a maximum of a twofold increase above normal levels a week after termination of the rhLIF treatment. No changes were seen in total and differential white blood cell counts in blood progenitor levels and in red blood cell numbers. The low- and medium-dose rhLIF treatments were tolerated without significant side effects. The animals treated with the high dose showed a reduction in body weight of approximately 10%. In conclusion, rhLIF was shown to stimulate APP and to increase the number of platelets in circulation in nonhuman primates.